Fetal Placenta Research Articles

Pharmacological Action of Baicalin on Gestational Diabetes Mellitus in Pregnant Animals Induced by Streptozotocin via AGE-RAGE Signaling Pathway.

Baicalin (BC) is a flavonoid reported to have various pharmacological activities, including antioxidant, anti-cancer, anti-inflammatory, anti-allergy, immune regulation, and anti-diabetic. This study examines the probable mechanism for gestational diabetes mellitus (GDM) brought on by streptozotocin (STZ) and the impact of BC on fetal development via AGEs (advanced serum glycation end products) and RAGE (the role of advanced glycation end products). STZ has been used in the current experimental study to induce diabetes mellitus in pregnant animals (gestational diabetes mellitus). GDM pregnant animals were separated into five groups and were treated with BC in a dose-dependent pattern for 19days. At the end of the experiment, the fetus and blood samples were drawn from all the pregnant rats to assess the biochemical parameter as well as AGE-RAGE. Administration of BC at varying doses leads to enhancement in the weight of the fetus body and placenta while gestational diabetic pregnant animals induced by STZ had a lower weight of the fetus body and placenta. The dose-dependent pattern of BC also enhanced fasting insulin (FINS), high-density lipoprotein (HDL), serum insulin, and hepatic glycogen. It also significantly enhanced the content of the antioxidant profile and pro-inflammatory cytokines and modulated the gene expression (VCAM- 1, p65, EGFR, MCP-1, 1NOX2, and RAGE) in various tissues in gestational diabetes mellitus pregnant rats. Baicalin demonstrated the potential impact on the embryo's development via the AGE-RAGE signaling pathway in STZ-induced GDM pregnant animals.

Causes of ovine abortion, vaccination protocols and uptake: an overview

Ovine abortion is a worldwide problem for sheep farmers, and can have a variety of infectious and non-infectious causes. The most notable infectious causes are Chlamydia abortus and Toxoplasma gondii, but there are a range of pathogens known to farmers and vets. Diagnosis is achieved by post-mortem examination of aborted lambs and testing of samples including, but not limited to, the foetal membranes and placenta. There are several efficacious vaccines available in the UK targeting abortion-associated pathogens, mainly to be administered before mating. Vaccine uptake is variable, and more emphasis on farmers complying with protocols needed.

Comparative steroid profiling of newborn hair and umbilical cord serum highlights the role of fetal adrenals, placenta, and pregnancy outcomes in fetal steroid metabolism

Previous steroid hormone studies concerning pregnancy and newborns have mainly focused on glucocorticoids; wider steroid profiles have been less commonly investigated. Here, we performed a comparative analysis of 17 steroids from newborn hair and umbilical cord serum at the time of delivery. The study participants (n=42, 50% girls) were a part of the Kuopio Birth Cohort and represent usual Finnish pregnancies. The hair and cord serum samples were analyzed with liquid chromatography high resolution mass spectrometry and triple quadrupole tandem mass spectrometry, respectively. We detected high individual variations in steroid hormone concentrations in both sample matrices. The concentrations of cortisol (F), corticosterone (B), estrone (E1), estradiol (E2), dehydroepiandrosterone (DHEA), 11β-hydroxyandostenedione (11bOHA4), 5α-androstanedione (DHA4), and 17α-hydroxypregnenolone (17OHP5) correlated positively between cord serum and newborn hair samples. In addition, F and 11bOHA4 concentrations correlated positively with each other in both newborn hair and cord serum samples. The cortisone-to-cortisol ratio (E/F) was significantly higher in cord serum than in newborn hair samples reflecting high placental 11βHSD2 enzyme activity. Only minor sex differences in steroid concentrations were observed; higher testosterone (T) and 11-deoxycortisol (S) with lower 11bOHA4 in male cord serum, and higher DHEA, androstenedione (A4) and 11bOHA4 in female newborn hair samples. Parity and delivery mode were the most significant pregnancy- and birth-related parameters associating with F and some other adrenocortical steroid concentrations. This study provides novel information about intrauterine steroid metabolism in late pregnancy and typical concentration ranges for several newborn hair steroids, including also 11-oxygenated androgens.

Microbial Profiling of Amniotic Fluid, Umbilical Blood and Placenta of the Foaling Mare.

The presence of a microbiome/microbiota in the placenta is hotly debated. In previous studies, the presence of bacteria in equine amniotic fluid and umbilical blood was independent of foal health. The objective of the present study was to determine if the same bacteria are present in the equine placenta as in amniotic fluid and umbilical blood. Samples were obtained from 24 parturient mares and foals. Placental bacterial DNA was extracted, and the microbiome was identified using 16S rRNA sequencing. All amniotic fluid samples contained some polymorphonucleocytes; bacteria were isolated from four samples. Aerobic or anaerobic growth was found in 18 and 3 umbilical blood samples, respectively. Serum amyloid A was <5 mg/L in all 24 samples, total WBC varied between 2900 and 10,700/µL, and fibrinogen varied between 0 and 5.16 g/L. In jugular blood, serum amyloid A was <5 mg/L in all 24 foals, total white blood count was 3200 to 8100/µL, and fibrinogen was 0.44 to 4.42 g/L. The diversity of bacterial microbiota was similar in all placental regions at the phylum level but differed at the genus level; the most abundant phyla were Proteobacteria (42-46.26%) and Actinobacteria (26.91-29.96%). In conclusion, bacteria were found in the fetal compartments and placenta of healthy equine pregnancies; however, we can neither prove nor disprove the hypothesis that the placenta has its own microbiome.

Two-Compartment Perfusion MR IVIM Model to Investigate Normal and Pathological Placental Tissue.

Perfusion and diffusion coexist in the placenta and can be altered by pathologies. The two-perfusion model, where f1 and, f2 are the perfusion-fraction of the fastest and slowest perfusion compartment, respectively, and D is the diffusion coefficient, may help differentiate between normal and impaired placentas. Investigate the potential of the two-perfusion IVIM model in differentiating between normal and abnormal placentas. Retrospective, case-control. 43 normal pregnancy, 9 fetal-growth-restriction (FGR), 6 small-for-gestational-age (SGA), 4 accreta, 1 increta and 2 percreta placentas. Diffusion-weighted-echo planar imaging sequence at 1.5 T. Voxel-wise signal-correction and fitting-controls were used to avoid overfitting obtaining that two-perfusion model fitted the observed data better than the IVIM model (Akaike weight: 0.94). The two-perfusion parametric-maps were quantified from ROIs in the fetal and maternal placenta and in the accretion zone of accreta placentas. The diffusion coefficient D was evaluated using a b ≥ 200 sec/mm2 -mono-exponential decay fit. IVIM metrics were quantified to fix f1 + f2 = fIVIM . ANOVA with Dunn-Sidák's post-hoc correction and Cohen's d test were used to compare parameters between groups. Spearman's coefficient was evaluated to study the correlation between variables. A P-value<0.05 indicated a statistically significant difference. There was a significant difference in f1 between FGR and SGA, and significant differences in f2 and fIVIM between normal and FGR. The percreta + increta group showed the highest f1 values (Cohen's d = -2.66). The f2 between normal and percreta + increta groups showed Cohen's d = 1.12. Conversely, fIVIM had a small effective size (Cohen's d = 0.32). In the accretion zone, a significant correlation was found between f2 and GA (ρ = 0.90) whereas a significant negative correlation was found between fIVIM and D (ρ = -0.37 in fetal and ρ = -0.56 in maternal side) and f2 and D (ρ = -0.38 in fetal and ρ = -0.51 in maternal side) in normal placentas. The two-perfusion model provides complementary information to IVIM parameters that may be useful in identifying placenta impairment. 2 TECHNICAL EFFICACY STAGE: 1.

Immunomodulatory role of decidual prolactin on the human fetal membranes and placenta.

The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment and protection against any infectious challenge. The fetal membranes and placenta create a hyperprolactinemic milieu in which prolactin (PRL) synthesized by the maternal decidua is transported through the amnion-chorion and accumulated into the amniotic cavity, where the fetus is bedded in high concentrations during pregnancy. PRL is a pleiotropic immune-neuroendocrine hormone with multiple immunomodulatory functions mainly related to reproduction. However, the biological role of PRL at the maternal-fetal interface has yet to be fully elucidated. In this review, we have summarized the current information on the multiple effects of PRL, focusing on its immunological effects and biological significance for the immune privilege of the maternal-fetal interface.

Gestational cadmium exposure disrupts fetal liver development via repressing estrogen biosynthesis in placental trophoblasts.

Cadmium (Cd), commonly found in diet and drinking water, is known to be harmful to the human liver. Nevertheless, the effects and mechanisms of gestational Cd exposure on fetal liver development remain unclear. Here, we reported that gestational Cd (150 mg/L) exposure obviously downregulated the expression of critical proteins including PCNA, Ki67 and VEGF-A in proliferation and angiogenesis in fetal livers, and lowered the estradiol concentration in fetal livers and placentae. Maternal estradiol supplement alleviated aforesaid impairments in fetal livers. Our data showed that the levels of pivotal estrogen synthases, such as CYP17A1 and 17β-HSD, was markedly decreased in Cd-stimulated placentae but not fetal livers. Ground on ovariectomy (OVX), we found that maternal ovarian-derived estradiol had no major effects on Cd-impaired development in fetal liver. In addition, Cd exposure activated placental PERK signaling, and inhibited PERK activity could up-regulated the expressions of CYP17A1 and 17β-HSD in placental trophoblasts. Collectively, gestational Cd exposure inhibited placenta-derived estrogen synthesis via activating PERK signaling, and therefore impaired fetal liver development. This study suggests a protective role for placenta-derived estradiol in fetal liver dysplasia shaped by toxicants, and provides a theoretical basis for toxicants to impede fetal liver development by disrupting the placenta-fetal-liver axis.

The Effect of Antiretroviral Therapy on Placenta Size and Fetal Development

HIV, or human immunodeficiency virus, is a virus that targets the human body’s immune system and weakens it so that it struggles to defend against other pathogens designed to harm the body. In order to enhance immune health and decrease the transmission of HIV, patients who have HIV are treated with antiretroviral therapy, or ART, a treatment that seeks to reduce the replication of HIV by disrupting a specific portion of the HIV replication cycle. However, while it does reduce the vertical transmission of HIV between mother and fetus, the use of antiretroviral therapy during pregnancy can have adverse impacts on the size of the placenta and the development of the fetus. Through the study of various research papers, a distinct connection between the use of antiretroviral therapy and the placenta size and fetal development was made. Analyzing the placenta and birth characteristics of fetuses from both women with and without HIV, overall the placentas of mothers with HIV taking ART drugs had smaller diameters, weights, and areas, along with an irregular shape, than mothers without HIV; the fetuses of mothers with HIV taking ART drugs had smaller weights at birth, weeks gestation at birth, and birth weight centile than fetuses of mothers without HIV. Exploring the impacts of antiretroviral therapy on placenta size and fetal development, this comprehensive research aims to assist researchers in creating safer and improved antiretroviral drugs to treat mothers with HIV that promote both the health of the mother and the development of the child.

Article Review on Histopathologic Features of Placenta and Adverse Outcome in Pregnant Women with COVID-19 Positive

<i>Introduction:</i> The placenta is the highly specialized organ of pregnancy that supports the normal growth and development of the fetus. During intrauterine fetal life placenta is the main metabolic, respiratory, excretory, and endocrine organ. Histologic features of normal placenta are differing according to the trimester of pregnancy. COVID-19 infection affects placenta and fetal membrane. Pregnant women with COVID-19 positive result in placental hyperfusion defects in maternal vessels and oxygenation in the intervillous space affecting perinatal outcome. <i>Methods:</i> Systematic reviews, meta-analysis, cross sectional and cohort studies were obtained through searches on PubMed, Medline, Science Direct, Google Scholar, library genesis, Scopus and Web of Science. Key words used for searching are “placenta”, “COVID-19”, “placenta development”, and “placenta histopathology”. <i>Result: </i>Total of 16 articles were included in this review. Many articles are reviewed whether the COVID-19 affects placenta histology and pregnancy adverse outcome in intrauterine life. Finally article which fulfills inclusion criteria are identified and reviewed. Review indicated that histopathologic features of placenta and adverse pregnancy outcome in COVID-19 confirmed pregnant women briefly. <i>Conclusion: </i>COVID-19 affects the placenta during pregnancy. Histopathologic findings of placenta in pregnant women with confirmed COVID-19 positive are fibrin deposition, micro classification, thrombus, avascular villi, infraction, and villous edema. Most common pregnancy adverse outcome are preterm birth, miscarriage and still birth.

The increased cfRNA of TNFSF4 in peripheral blood at late gestation and preterm labor: its implication as a noninvasive biomarker for premature delivery.

Given the important roles of immune tolerance and inflammation in both preterm and term labor, some inflammation-related genes could be related to the initiation of labor, even preterm labor. Inspection of cell-free RNA (cfRNA) engaged in inflammation in maternal blood may represent the varied gestational age and may have significant implications for the development of noninvasive diagnostics for preterm birth. To identify potential biomarkers of preterm birth, we investigated the cfRNA and exosomal miRNA in the peripheral blood of pregnant women at different gestational ages that undergo term labor or preterm labor. 17 inflammatory initiation-related cfRNAs were screened by overlapping with the targets of decreasing miRNAs during gestation and highly expressed cfRNAs at late gestation in maternal blood. To reveal the origins and mechanisms of these screened cfRNAs, the datasets of single-cell RNA sequencing from peripheral blood mononuclear cells of pregnant women, the fetal lung, and the placenta across different gestational ages were analyzed. During late gestation, TNFSF4 expression increased exclusively in pro-inflammatory macrophages of maternal blood, whereas its receptor, TNFRSF4, increased expression in T cells from the decidua, which suggested the potential cell-cell communication of maternally-originated pro-inflammatory macrophages with the decidual T cells and contributed to the initiation of labor. Additionally, the cfRNA of TNFSF4 was also increased in preterm labor compared to term labor in the validation cohorts. The EIF2AK2 and TLR4 transcripts were increased in pro-inflammatory macrophages from both fetal lung and placenta but not in those from maternal mononuclear cells at late gestation, suggesting these cfRNAs are possibly derived from fetal tissues exclusively. Moreover, EIF2AK2 and TLR4 transcripts were found highly expressed in the pro-inflammatory macrophages from decidua as well, which suggested these specific fetal-origin macrophages may function at the maternal-fetal interface to stimulate uterine contractions, which have been implicated as the trigger of parturition and preterm labor. Taken together, our findings not only revealed the potential of peripheral TNFSF4 as a novel cfRNA biomarker for noninvasive testing of preterm labor but further illustrated how maternal and fetal signals coordinately modulate the inflammatory process at the maternal-fetal interface, causing the initiation of term or preterm labor.

Virtual touch IQ elastography in the evaluation of fetal liver and placenta in pregnancies with gestational diabetes mellitus.

Elastography is considered a novel technique in the assessment of placenta parenchymal elasticity and very few data present the feasibility of elastography on human fetal tissue. This study aims to investigate the feasibility of fetal liver and placenta elastography and differences in pregnancies with GDM. Fifty-five women with GDM and 40 women with uncomplicated pregnancy as the control group was enrolled prospectively in this case-control study. Fetal liver VTIQ and placenta VTIQ elastography were performed between 25 and 39weeks of pregnancy. Mean placenta thickness at the level of umbilical cord insertion was significantly higher in the GDM group than in the control group (p=0.034). VTIQ elastography elasticity velocity (kPa) examinations revealed similar mean placenta and mean fetal liver stiffness in both groups. A weak to moderate correlation was observed between the mean elasticity of the placenta and the mean elasticity of the fetal liver (r=0.310; p=0.004). Elastography may provide valuable information of especially on fetal tissue development and pathology. While placenta and fetal liver VTIQ elastography are feasible in pregnancy, the diagnostic value of these examinations inGDM is not certain and it seems to be that significant differences in SWE examinations that reflect structural changes in fetal tissue or placenta are more prominent in more chronic conditions such as type 1 and type 2 diabetes mellitus.

The Trace Element Concentrations and Oxidative Stress Parameters in Afterbirths from Women with Multiple Pregnancies.

The aim of this study was to evaluate the intensity of oxidative stress by measuring the concentrations of lipid peroxidation products (LPO) in fetal membrane, umbilical cord, and placenta samples obtained from women with multiple pregnancies. Additionally, the effectiveness of protection against oxidative stress was assessed by measuring the activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR). Due to the role of iron (Fe), copper (Cu), and zinc (Zn) as cofactors for antioxidant enzymes, the concentrations of these elements were also analyzed in the studied afterbirths. The obtained data were compared with newborn parameters, selected environmental factors, and the health status of women during pregnancy to determine the relationship between oxidative stress and the health of women and their offspring during pregnancy. The study involved women (n = 22) with multiple pregnancies and their newborns (n = 45). The Fe, Zn, and Cu levels in the placenta, umbilical cord, and fetal membrane were determined using inductively coupled plasma atomic emission spectroscopy (ICP-OES) using an ICAP 7400 Duo system. Commercial assays were used to determine SOD, GPx, GR, CAT, and LPO activity levels. The determinations were made spectrophotometrically. The present study also investigated the relationships between trace element concentrations in fetal membrane, placenta, and umbilical cord samples and various maternal and infant parameters in women. Notably, a strong positive correlation was observed between Cu and Zn concentrations in the fetal membrane (p = 0.66) and between Zn and Fe concentrations in the placenta (p = 0.61). The fetal membrane Zn concentration exhibited a negative correlation with shoulder width (p = -0.35), while the placenta Cu concentration was positively correlated with placenta weight (p = 0.46) and shoulder width (p = 0.36). The umbilical cord Cu level was positively correlated with head circumference (p = 0.36) and birth weight (p = 0.35), while the placenta Fe concentration was positively correlated with placenta weight (p = 0.33). Furthermore, correlations were determined between the parameters of antioxidative stress (GPx, GR, CAT, SOD) and oxidative stress (LPO) and the parameters of infants and maternal characteristics. A negative correlation was observed between Fe and LPO product concentrations in the fetal membrane (p = -0.50) and placenta (p = -0.58), while the Cu concentration positively correlated with SOD activity in the umbilical cord (p = 0.55). Given that multiple pregnancies are associated with various complications, such as preterm birth, gestational hypertension, gestational diabetes, and placental and umbilical cord abnormalities, research in this area is crucial for preventing obstetric failures. Our results could serve as comparative data for future studies. However, we advise caution when interpreting our results, despite achieving statistical significance.

The Influence of Fetal Sex on Antepartum Treatments in a Murine Model of Preterm Birth [ID: 2369702

INTRODUCTION: Preterm neonates exposed to magnesium sulfate (MgSO4) and corticosteroids such as betamethasone (BMTZ) in utero have a lower incidence of neurodevelopmental disability, specifically cerebral palsy. The efficacy of MgSO4/BMTZ remains poor, particularly in male offspring. The mechanisms by which MgSO4/BMTZ confer “neuroprotection” in only some patients and in relation to fetal sex, remain unknown. Our objective was to examine sex-specific responses to MgSO4/BMTZ in a murine model of fetal neuroinflammatory injury. METHODS: Utilizing an established murine model of preterm birth, dams were injected intrauterine with either phosphate-buffered saline or bacterial endotoxin (lipopolysaccharide [LPS]) on embryonic day 15.5 to induce fetal inflammation. Thereafter, dams received MgSO4/BMTZ or the vehicle. Fetal brains and placentas were collected 6 hours postinjection for gene expression analysis of key inflammatory cytokines: Il1b, Il6, and Tnf. RESULTS: Irrespective of sex, LPS exposure up-regulated all three cytokines. With MgSO4/BMTZ, Il1b expression was significantly lower in female, but not male brains. In contrast, MgSO4/BMTZ lowered Il6 expression in placentas from males, but not females. No sex differences were observed with Tnf expression. CONCLUSION: Within the context of LPS-mediated in utero inflammation, fetal sex influenced the efficacy of MgSO4/BMTZ. The anti-inflammatory effect of MgSO4/BMTZ also appeared tissue specific, with protection shown in female brains and male placentas. These results suggest that the neuroprotective effects of MgSO4/BMTZ are more robust in females, whereas placental inflammation is more affected in males. Further investigation is warranted to determine whether these sex-specific patterns govern fetal outcomes.

LPCAT1 levels in the placenta, the maternal plasma and the fetal plasma do not predict fetal lung responses to glucocorticoids in a sheep model of pregnancy

Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is important for saturated phosphatidylcholine (Sat-PC) production in the lung. Sat-PC is a critical component of pulmonary surfactant, which maintains low alveolar surface tension, facilitating respiration. Previous studies have reported an association between maternal and fetal LPCAT1 levels and neonatal lung function. Using a sheep model of pregnancy, we investigated a potential correlation between glucocorticoid-induced lung maturation and LPCAT1 mRNA and/or protein levels in the fetal lung, the placenta, the fetal plasma, and the maternal plasma. Eighty seven single pregnant ewes received maternal intramuscular injections of betamethasone. A sub-group of five animals had both maternal and fetal catheters installed to allow for sequential sampling from both plasma compartments. Lambs were surgically delivered under terminal anaesthesia between 2 and 8 days after initial ANS treatment, at a gestational age of 121-123 days. Lambs were ventilated for 30min to determine functional lung maturation before being euthanized for necropsy and sample collection. Fetal lung, placenta, and fetal and maternal plasma samples were used to analyse LPCAT1 gene expression and protein levels. The expression of LPCAT1 mRNA in the fetal lung was significantly corelated to Sat-PC levels at 8 days (R2=0.23, p<0.001) and lung maturation status overall (gas exchange efficiency as determined by measurements of lamb PaCO2 during ventilation, R2=0.20, p<0.001). Similarly, fetal lung LPCAT1 mRNA was also significantly correlated with the individual durability of ANS effects on fetal lung maturation (R2=0.20, p<0.001). Although ANS therapy altered LPCAT1 mRNA expression in the placenta, observed changes were independent of fetal lung maturation outcomes. Neither maternal nor fetal plasma LPCAT1 levels were changed by ANS therapy over the period, including in analysis of serial maternal and fetal samples from chronically catheterised animals. LPCAT1 expression in the fetal lung was associated with the durability of glucocorticoid effects on fetal lung maturation. However, LPCAT1 expression in the placenta, the fetal plasma, and the maternal plasma was neither associated with, nor predictive of fetal lung maturation after glucocorticoid treatment in a sheep model of pregnancy.

Comparison of Prenatal and Postmortem Diagnoses from 251 Fetal Autopsies: High Rate of Placenta Pathologies, Low Rate of Discrepancies

Background: In cases of intrauterine fetal death (IUFD), autopsy and placenta pathology can provide additional information to sonographic findings. We assessed the frequency of prenatally missed relevant diagnoses. Materials and methods: A retrospective evaluation of fetal autopsies from 2006 to 2021 was performed and were classified as: i) agreement, ii) cases where autopsy revealed additional findings, or iii) postmortem findings which changed the diagnosis. Results: A total of 199/251 spontaneous IUFD and 52/251 induced abortions were included. In spontaneous IUFD, placenta pathologies were the leading cause of death (89%). Full agreement was found in most cases (91% and 87% in spontaneous IUFD and induced abortion, respectively), while additional findings (7% and 12%) and major discrepancies (each 2%) were detected less frequently. Conclusion: In some cases where major findings were missed, autopsy could establish a diagnosis.

Diagnosis of Pregnancy Complications Using Blind Ultrasound Sweeps Performed by Individuals Without Prior Formal Ultrasound Training.

To estimate the diagnostic accuracy of blind ultrasound sweeps performed with a low-cost, portable ultrasound system by individuals with no prior formal ultrasound training to diagnose common pregnancy complications. This is a single-center, prospective cohort study conducted from October 2020 to January 2022 among people with second- and third-trimester pregnancies. Nonspecialists with no prior formal ultrasound training underwent a brief training on a simple eight-step approach to performing a limited obstetric ultrasound examination that uses blind sweeps of a portable ultrasound probe based on external body landmarks. The sweeps were interpreted by five blinded maternal-fetal medicine subspecialists. Sensitivity, specificity, and positive and negative predictive values for blinded ultrasound sweep identification of pregnancy complications (fetal malpresentation, multiple gestations, placenta previa, and abnormal amniotic fluid volume) were compared with a reference standard ultrasonogram as the primary analysis. Kappa for agreement was also assessed. Trainees performed 194 blinded ultrasound examinations on 168 unique pregnant people (248 fetuses) at a mean of 28±5.85 weeks of gestation for a total of 1,552 blinded sweep cine clips. There were 49 ultrasonograms with normal results (control group) and 145 ultrasonograms with abnormal results with known pregnancy complications. In this cohort, the sensitivity for detecting a prespecified pregnancy complication was 91.7% (95% CI 87.2-96.2%) overall, with the highest detection rate for multiple gestations (100%, 95% CI 100-100%) and noncephalic presentation (91.8%, 95% CI 86.4-97.3%). There was high negative predictive value for placenta previa (96.1%, 95% CI 93.5-98.8%) and abnormal amniotic fluid volume (89.5%, 95% CI 85.3-93.6%). There was also substantial to perfect mean agreement for these same outcomes (range 87-99.6% agreement, Cohen κ range 0.59-0.91, P<.001 for all). Blind ultrasound sweeps of the gravid abdomen guided by an eight-step protocol using only external anatomic landmarks and performed by previously untrained operators with a low-cost, portable, battery-powered device had excellent sensitivity and specificity for high-risk pregnancy complications such as malpresentation, placenta previa, multiple gestations, and abnormal amniotic fluid volume, similar to results of a diagnostic ultrasound examination using a trained ultrasonographer and standard-of-care ultrasound machine. This approach has the potential to improve access to obstetric ultrasonography globally.

Effects of prenatal pesticide exposure on the fetal brain and placenta transcriptomes in a rodent model

Organophosphate and pyrethroid pesticides are among the most extensively used insecticides worldwide. Prenatal exposures to both classes of pesticides have been linked to a wide range of neurobehavioral deficits in the offspring. The placenta is a neuroendocrine organ and the crucial regulator of the intrauterine environment; early-life toxicant exposures could impact neurobehavior by disrupting placental processes. Female C57BL/6J mice were exposed via oral gavage to an organophosphate, chlorpyrifos (CPF) at 5mg/kg, a pyrethroid, deltamethrin (DM), at 3mg/kg, or vehicle only control (CTL). Exposure began two weeks before breeding and continued every three days until euthanasia at gestational day 17. The transcriptomes of fetal brain (CTL n=18, CPF n=6, DM n=8) and placenta (CTL n=19, CPF n=16, DM n=12) were obtained through RNA sequencing, and resulting data was evaluated using weighted gene co-expression networks, differential expression, and pathway analyses. Fourteen brain gene co-expression modules were identified; CPF exposure disrupted the module related to ribosome and oxidative phosphorylation, whereas DM disrupted the modules related to extracellular matrix and calcium signaling. In the placenta, network analyses revealed 12 gene co-expression modules. While CPF exposure disrupted modules related to endocytosis, Notch and Mapk signaling, DM exposure dysregulated modules linked to spliceosome, lysosome and Mapk signaling pathways. Overall, in both tissues, CPF exposure impacted oxidative phosphorylation, while DM was linked to genes involved in spliceosome and cell cycle. The transcription factor Max involved in cell proliferation was overexpressed by both pesticides in both tissues. In summary, gestational exposure to two different classes of pesticide can induce similar pathway-level transcriptome changes in the placenta and the brain; further studies should investigate if these changes are linked to neurobehavioral impairments.

Prenatal Stress Induces Translational Disruption Associated with Myelination Deficits

Disruptions to neurodevelopment are known to be linked to behavioral disorders in childhood and into adulthood. The fetal brain is extremely vulnerable to stimuli that alter inhibitory GABAergic pathways and critical myelination processes, programing long-term neurobehavioral disruption. The maturation of the GABAergic system into the major inhibitory pathway in the brain and the development of oligodendrocytes into mature cells capable of producing myelin are integral components of optimal neurodevelopment. The current study aimed to elucidate prenatal stress-induced mechanisms that disrupt these processes and to delineate the role of placental pathways in these adverse outcomes. Pregnant guinea pig dams were exposed to prenatal stress with strobe light exposure for 2 h/day on gestational age (GA) 35, 40, 45, 50, 55, 60, and 65, and groups of fetuses and placentae were collected after the stress exposure on GA40, GA50, GA60, and GA69 (term). Fetal plasma, placental, and brain tissue were collected for allopregnanolone and cortisol quantification with ELISA. Relative mRNA expression of genes of specific pathways of interest was examined with real-time PCR in placental and hippocampal tissue, and myelin basic protein (MBP) was quantified immunohistochemically in the hippocampus and surrounding regions for assessment of mature myelin. Prenatal stress in mid-late gestation resulted in disruptions to the translational machinery responsible for the production of myelin and decreased myelin coverage in the hippocampus and surrounding regions. The male placenta showed an initial protective increase in allopregnanolone concentrations in response to maternal psychosocial stress. The male and female placentae had a sex-dependent increase in neurosteroidogenic enzymes at term following prenatal stress. Independent from exposure to prenatal stress, at gestational day 60 – a critical period for myelin development, the placentae of female fetuses had increased capability of preventing cortisol transfer to the fetus through expression of 11-beta-hydroxysteroid dehydrogenase types 1 and 2. The deficits early in the process of maturation of myelination indicate that the reduced myelination observed at childhood equivalence in previous studies begins in fetal life. This negative programing persists into childhood, potentially due to dysregulation of MBP translation processes. Expression patterns of neurosteroidogenic enzymes in the placenta at term following stress may identify at-risk fetuses that have been exposed to a stressful in utero environment.

Composition and Biological Activity of Fetoplacental Tissues-Derived Cryoextracts Being Differently Obtained

The protein-peptide composition of fetal tissues (FTCEs) and placenta (PCE) cryoextracts of rats was investigated by gel permeation chromatography. Cryoextracts were derived from tissue homogenates using the freeze-warming modes: 1 – single (–20°С); 2 – double (–20; –196°С) and 3 – triple (–20; –196; –196°С) ones. The biological activity of cryoextracts was in vitro evaluated by the phagocytic activity of neutrophil granulocytes (NG) of the blood of intact rats after incubation with an inactivated culture of Staphylococcus aureus (2 × 109 cells/ml) for 45 and 120 min for the concentrations of extracts in the incubation medium: 1.6; 3.1; 6 mg/ml in terms of dry substance. The use of mode 3 ensured a greater yield of total protein and low molecular weight compounds of a protein-peptide nature in the composition of cryoextracts. The content of low-molecular-weight fractions in FTCE exceeded that in PCE, regardless of the obtaining mode. Incubation of NG with cryoextracts did not significantly increase the number of neutrophils which entered into phagocytosis. However, all the samples of PCE and FTCE were characterized by a dose-dependent rise in the NG absorption activity during the 45-minute incubation compared to the control.

MYH3-associated non-syndromic palatoschisis (cleft palate,CP) in Limousine cattle.

MYH3-associated non-syndromic palatoschisis (cleft palate,CP) in Limousine cattle.